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Easily accessible and accurate biomarkers can aid Parkinson's disease diagnosis. We investigated whether combining plasma levels of α-synuclein, anti-α-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (Aβ40) is novel. Plasma levels of biomarkers were quantified with ELISA. Using receiver operating characteristic (ROC) curve analysis, levels of α-synuclein, anti-α-synuclein, and their ratios with Aβ40 were analyzed in an initial training set of cases and controls. Promising biomarkers were then used to build a diagnostic algorithm. Verification of the results of biomarkers and the algorithm was performed in an independent set. The training set consisted of 50 cases (age 65.2±9.3, range 44-83, female:male=21:29) with 50 age- and gender-matched controls (67.1±10.0, range 45-96 years; female:male=21:29). ROC curve analysis yielded the following area under the curve results: anti-α-synuclein=0.835, α-synuclein=0.738, anti-α-synuclein/Aβ40=0.737, and α-synuclein/Aβ40=0.663. A 2-step diagnostic algorithm was built: either α-synuclein or anti-α-synuclein was ≥2 times the means of controls (step-1), resulting in 74% sensitivity; and adding α-synuclein/Aβ40 or anti-α-synuclein/Aβ40 (step-2) yielded better sensitivity (82%) while using step-2 alone yielded good specificity in controls (98%). The results were verified in an independent sample of 46 cases and 126 controls, with sensitivity reaching 91.3% and specificity 90.5%. The algorithm was equally sensitive in Parkinson's disease of ≤5-year duration with 92.6% correctly identified in the training set and 90% in the verification set. With two independent samples totaling 272 subjects, our study showed that combination of biomarkers of α-synuclein, anti-α-synuclein, and their ratios to Aβ40 showed promising sensitivity and specificity.

To share our experience of establishing an acute outreach service to nursing homes and to evaluate the impact of such service on emergency department presentations, data were drawn from a pre-existing database from 2013 to 2017. Of the 986 acute patients treated in 12 nursing homes over a 23-month period, the acute geriatric outreach service was shown to be safe, with few adverse events (one allergic reaction) and 5.3% of patients required transfer to hospital. The acute service decreased emergency department presentation of nursing home patients by 10% compared to the subacute service (incidence rate ratio = 0.90; 95% confidence interval: 0.84-0.96; P = 0.001). Cost-benefit analysis showed for every $1 spent, a saving of $5 was realised.

Eighty consecutive Chinese patients diagnosed with Alzheimer disease were assessed for darkening of grey hair. Of the 62 eligible patients (mean age = 79.3 ± 7.9 years; male: female = 1:1.48), 24/62 (38.7%, 95%CI: 26.6 – 51.9) reported hair darkening after prolonged usage of cholinesterase inhibitor for at least 6 months. Of the 24 patients with hair darkening, 17 (70.9%) experienced hair darkening in the occipital region, 3 (12.5%) in the parietal region, 2 (8.3%) patients in the frontal region and 2 (8.3%) patients experienced hair darkening in multiple regions. Analysis of melanin concentration showed no significant difference between darkened hair of patients after prolonged drug use and the dark hair of controls (P = 0.381).

Background The most effective and efficient model for providing organized stroke care remains uncertain. This study aimed to compare the effect of two models in a randomized controlled trial. Methods Patients with acute stroke were randomized on day one of admission to combined, co-located acute/rehabilitation stroke care or traditionally separated acute/rehabilitation stroke care. Outcomes measured at baseline and 90 days post-discharge included functional independence measure, length of hospital stay, and functional independence measure efficiency (change in functional independence measure score ÷ total length of hospital stay). Results Among 41 patients randomized, 20 were allocated co-located acute/rehabilitation stroke care and 21 traditionally separated acute/rehabilitation stroke care. Baseline measurements showed no significant difference. There was no significant difference in functional independence measure scores between the two groups at discharge and again at 90 days postdischarge (co-located acute/rehabilitation stroke care: 103·6 ± 22·2 vs. traditionally separated acute/rehabilitation stroke care: 99·5 ± 27·7; P = 0·77 at discharge; co-located acute/rehabilitation stroke care: 109·5 ± 21·7 vs. traditionally separated acute/rehabilitation stroke care: 104·4 ± 27·9; P= 0·8875 at 90 days post-discharge). Total length of hospital stay was 5·28 days less in co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (24·15 ± 3·18 vs. 29·42 ± 4·5, P = 0·35). There was significant improvement in functional independence measure efficiency score among participants assigned to co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (co-located acute/rehabilitation stroke care: median 1·60, interquartile range: 0·87–2·81; traditionally separated acute/rehabilitation stroke care: median 0·82, interquartile range: 0·27–1·57, P = 0·0393). Linear regression analysis revealed a high inverse correlation ( R2 = 0·89) between functional independence measure efficiency and time spent in the acute stroke unit. Conclusion This proof-of-concept study has shown that co-located acute/rehabilitation stroke care was just as effective as traditionally separated acute/rehabilitation stroke care as reflected in functional independence measure scores, but significantly more efficient as shown in greater functional independence measure efficiency. Co-located acute/rehabilitation stroke care has potential for significantly improved hospital bed utilization with no patient disadvantage.

In this study, we aimed to determine the factors associated with recurrent falls in aged-care inpatients at a tertiary hospital, with a focus on the cognitive domains of recurrent fallers. We retrospectively examined the characteristics of 70 aged-care inpatients who sustained ≥ 2 falls; 269 patients who sustained 1 fall; and 69 non-fallers during their hospital admission. We also analyzed the available Mini-Mental State Examination (MMSE) scores and sub-scores of 37 recurrent fallers, 163 single fallers, and 37 non-fallers. The independent risk factors for recurrent falls were a history of dementia, stroke, or atrial fibrillation; and patients' hospital length of stay5 weeks. Protective factors were the patients' ability to speak English and a history of depression. Recurrent fallers had significantly lower MMSE scores than single fallers and non-fallers (17.3 ± 6.7, 20.2 ± 6.2, 24.0 ± 5.1, respectively, p0.01); and a larger proportion of recurrent fallers had MMSE18 than in the other two groups (54.1%, 34.4% and 10.8%, respectively, p0.01). In addition, patients with recurrent falls were more likely to have significantly lower scores in the 'registration', 'attention and calculation', 'recall' and 'praxis' domains of the MMSE than single fallers. The findings from this study suggest that cognitive impairment particularly affecting short-term memory, recall and visuospatial perception may contribute to recurrent falls in the inpatient population. Prospective studies to elucidate a causal relationship may be worthwhile.

An increasing body of research suggests that a number of immune mechanisms play a role in degenerative pathways in Parkinson's disease (PD). In the current work we investigated a posited humoral immune response in this disorder. Sera from PD patients exhibited a significantly enhanced absorbance response on a novel ELISA for anti-melanin antibodies, compared to sera from age-matched control subjects. The enhanced ELISA absorbance response was specific for catecholamine-based melanins and was unrelated to antiparkinsonian dopaminergic medication. Further, the absorbance response was significantly and negatively correlated with disease duration. These data suggest that a specific humoral anti-melanin antibody response is present in PD and is more active in early disease. While the contribution of this novel immune response to the initiation and progression of this disorder is unclear, this finding supports the hypothesis that specific immune responses occurring in PD may respond to therapeutic interventions in this disorder.

STUDY OBJECTIVE - Nested case-control study aimed to assess the quality of life of community dwelling participants aged 65 years or over with newly diagnosed Essential Tremor (ET). METHODS AND RESULTS - Thirty-two participants with newly diagnosed ET and 32 age and gender matched controls were administered the Rand-SF36 quality of life questionnaire. Medical co-morbidities were also assessed in the two groups. Results - Participants with ET had significantly lower scores in the physical function, role limitation because of physical function, role limitation as a result of emotional problem, pain, and energy/vitality subscales of the Rand-SF36 when compared with controls. CONCLUSIONS - Older patients with newly diagnosed ET have poorer quality of life than their community dwelling counterparts without ET.

Summary Objective To review the severe acute respiratory syndrome (SARS) epidemic in Beijing using basic epidemiological principles omitted from the original analysis. Study design Analysis of Prospective surveillance data for Beijing collected during the outbreak. Methods Surveillance data were reclassified according to World Health Organization criteria. Cases previously excluded without date of onset of illness were included in the epidemic curve from estimates using the average time between date of onset and date of hospitalization for cases with both dates. Cases who failed to give a contact history were now included; 7% ( n = 5 ) of cases during the import phase and 61% ( n = 365 ) during the peak phase. Previously excluded cases were included for plotting on an epidemic curve, and basic spot mapping for distribution of cases was used from attack rates recalculated for age, gender, occupation, residential location, date of onset of illness and demographics. Results The spot map effectively illustrated clusters by residency, with the inner-city sustaining the highest attack rate (33.42 per 100,000), followed by an easterly distribution 5–30 km away (21.62 per 10,000), and lowest in districts 60–160 km away (9.21 per 100,000). The new epidemic curve shows the outbreak commencing 10 days earlier than initially reported, with a three-fold greater increase in cases during the escalation phase than previously estimated. Conclusion In hindsight, the investigation of the Beijing SARS would have benefited from the use of spot maping as an essential outbreak tool for early identification of specific geographical area(s) for quarantining. If a spot map of incidence density rates was used during the early phase of the outbreak, the inner city might have been identified as a major risk factor requiring rapid quarantining. Contact history became uncommon as the outbreak progressed, suggesting that hospitals were over-burdened or pathogenesis and environment risk factors changed, strengthening the usefulness of early spot mapping and the need to modify risk factors included as contact history as the epidemic progresses.

Mutations in the parkin gene are the major cause of autosomal recessive early-onset forms of Parkinson's disease (PD). As reduced parkin expression might also affect the clinical course of idiopathic PD we investigated the effect of a low expressing allele in the parkin promoter region on the age at disease onset (AAO). Patients with PD (n=175) fulfilling standard diagnostic criteria were recruited by experienced neurologists at two movement disorders clinics in Sydney and Brisbane, Australia. DNA was extracted from whole blood and the -258 T/G polymorphism genotyped using PCR/RFLP. AAO effects were analysed using univariate ANOVA, binomial logistic regression modelling and Kaplan-Meier survival analysis. Subjects with the GG genotype (n=10, mean AAO=46.2+/-11.5 (S.D.) years) had a significantly lower mean AAO compared to the common TT genotype (n=104, mean AAO=56.1+/-12.7, p=0.02). There was no difference in mean AAO between the TT and TG individuals (n=61, mean AAO=55.3+/-11.6). Stratifying the sample by median AAO (55 years) revealed that the GG genotype was over-represented in the early-onset group (n=9, OR=18.6, 95% CI=1.41-245.3, p=0.03). We speculate that reduced expression of normal parkin protein may result in an early manifestation of PD symptoms.

Falls are a common problem in the elderly. A common error in their management is that injury from the fall is treated, without finding its cause. Thus a proactive approach is important to screen for the likelihood of fall in the elderly. Fall assessment usually includes a focused history and a targeted examination. Timed up-and-go test can be performed quickly and is able to predict the likelihood of fall. Evidence-based fall prevention interventions include multi-component group or home-based exercises, participation in Tai Chi, environmental modifications, medication review, management of foot and footwear problems, vitamin D supplementation, and management of cardiovascular problems. If possible, these are best implemented in the form of multifactorial intervention. Bone health enhancement for residential care home residents and appropriate community patients, and prescription of hip protectors for residential care home residents are also recommended. Multifactorial intervention may also be useful in a hospital and residential care home setting. Use of physical restraints is not recommended for fall prevention.

Background: Coagulation disorders are seen in cancer patients, but it is not clear whether cancer predisposes stroke patients to unique characteristics. The aim of the study was to investigate risk factors, pattern,etiology and outcome in stroke patients with cancer. Methods: A retrospective review of all ischemic stroke (IS) patients with cancer (n = 56) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted and comparison made to age- and gender-matched noncancer IS patients admitted to the same hospital during the same period. Results: Vascular risk factors and stroke pattern were comparable in cancer and noncancer groups. Poststroke thrombotic episodes (myocardial infarction, deep vein thrombosis or pulmonary emboli) were more common in the cancer group than in the noncancer group (11 vs. 0%, p = 0.031). Depression was also more common in the cancer group than in the noncancer group (14 vs. 2%, p = 0.039). There was a tendency for more patients in the cancer group to die in hospital (30 vs. 14%, p = 0.078). Conclusions: Coagulation disorders were more likely to be seen in stroke cancer patients, and patients with cancer tended to have a higher in-hospital poststroke mortality. Larger sample size studies may identify further differences in the characteristics of stroke patients with cancer.

Objective – To investigate risk factors, stroke pattern and outcome in stroke patients with cancer. Methods – A retrospective review of all stroke patients with cancer (n = 69) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted, and comparison made to age- and gender-matched non-cancer stroke patients admitted to the same hospital during the same period. Results – Vascular risk factors did not significantly differ between cancer and non-cancer groups. There was a trend towards greater risk of intracerebral haemorrhage in the cancer group vs the non-cancer group. Previous deep vein thrombosis was more common, and prothrombin time and activated partial thromboplastin time were prolonged in the cancer group vs the non-cancer group. More patients died in hospital in the cancer group vs the non-cancer group. Conclusions – Coagulation disorders are more likely to be seen in stroke patients with cancer, and patients with cancer have a higher in-hospital post-stroke mortality.

We provided data to show that the transcriptional activity of wildtype -258T in the parkin promoter region was significantly higher than the -258G variant in human cell lines. The transcriptional activity of wildtype -258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the -258G variant. The transcriptional upregulation was significantly higher for wildtype -258T compared to -258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter -258G variant was associated with an increased risk of sporadic Parkinson's disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant may have a higher risk of developing PD.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p < 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD.

This study examined stroke risk factor profiles, management and outcomes for elderly patients with English-speaking background (ESB) and non-English-speaking background (NESB). This is an observational cohort study with both retrospective and prospective components. In total, 186 consecutive acute stroke patients aged ≧65 years admitted to our hospital were recruited over a 12-month period. Patient characteristics, stroke risk factors and management, in-hospital mortality, functional independence measurement scores before admission and at discharge, and discharge destination were recorded. On admission, NESB patients with atrial fibrillation (AF) were less likely to be taking warfarin than ESB patients (1 out of 19 with NESB vs. 19 out of 41 with ESB, p = 0.001). More NESB patients had a history of diabetes mellitus (DM) than ESB patients (41.4 vs. 10.2%, respectively; p = 0.001). However, ESB and NESB patients were comparable in terms of age, gender, preadmission functional status as well as other stroke risk factors (including smoking and alcohol drinking pattern, prevalence of hypertension and lipid disorder) and their management. In-hospital mortality was similar between ESB and NESB patients (10.2 vs. 8.6%). In conclusion, we found an association with our population of elderly NESB patients and an underutilization of warfarin for AF as well as a higher frequency of DM. Determination of the underlying reasons for such differences may be of value in the primary health care of NESB patients.

Background: The slow acetylator genotype for N -acetyltransferase 2 ( NAT2 genotype) may be associated with PD in white subjects and the genotype is common in both white and Chinese populations. Whether there is a relationship between NAT2 genotype and PD in Chinese subjects is not known. Objective: To investigate the association between the slow acetylator genotype for N -acetyltransferase 2 and PD in a Chinese population. Methods: The authors obtained DNA samples and documented sex, age, and smoking history in 99 Chinese patients with PD and in 126 control subjects from two major Hong Kong hospitals. PCR–restriction fragment length polymorphism was used to identify M1 , M2 , and M3 mutant polymorphisms of the slow acetylator genotype for N -acetyltransferase 2. Logistic regression analyses were carried out to investigate the relationships between the different variables and PD. Results: The frequency of the slow acetylator genotype for N -acetyltransferase 2 in the PD group was significantly higher than that of the control group (68.7% vs 28.6%) with an OR of 5.53 (95% CI 3.08 to 9.92) after adjusting for age, sex, and smoking history. In a subgroup analysis smoking had no modifying effect on the association between genotype and PD. Conclusions: There is a significant association between PD and the slow acetylator genotype for N -acetyltransferase 2 in Hong Kong Chinese. The OR found is among the highest reported so far in all susceptibility gene studies for PD in both Chinese and white subjects and provides evidence for a possible functional relationship between NAT2 slow acetylator genotype and PD in both racial groups.

The frequency of LRRK2 Gly2385Arg mutation in Hong Kong Chinese with early-onset (ageor =45 years) Parkinson's disease was identified and compared with late-onset patients (age50 years) and controls. The mutation prevalence were 8.8, 8.3, and 0% for early-onset, late-onset, and controls, respectively. The mean age of onset among LRRK2 G2385R carriers was 42.7 years old for early-onset compared to 74.3 for late-onset patients. LRRK2 G2385R mutation appears to be as prevalent among early-onset as late-onset patients.

For people at high risk of hip fracture living in community settings, providing hip protectors at no cost increased adherence, but the additional effect of an educational programme was limited. Overall, the level of adherence was modest.The objective of the study was to increase adherence with hip protector use by older people at high risk of hip fracture. The study included two randomised controlled trials with 308 older people recruited from three hospital rehabilitation wards and 171 older people recruited from the community.Participants were randomised into three groups. The control group received a brochure about hip protectors. The no cost group were fitted with free hip protectors and asked to use them. The combined group received free hip protectors and education sessions about their use. Adherence with the use of hip protectors at 3 and 6 months after recruitment was measured. Secondary outcomes were falls, fractures and hospitalisations.Very few participants in the two control groups bought a hip protector. Overall adherence in the four intervention groups was modest, but higher in the community recruitment setting (49%) than in the hospital recruitment setting (36%) at 6 months. In the community recruitment group, at 3 months of follow-up, a significantly higher number of participants in the combined group (62%) were wearing hip protectors compared to the no cost group (43%, p=0.04). Five hip fractures occurred during the study, with four sustained whilst not wearing the hip protectors.Providing hip protectors at no cost to community living older people at high risk of hip fractures modestly increases initial acceptance and adherence with hip protector use. Additional education may further increase hip protector use in people living in the community in the short term.

Objectives To test different adherent strategies aimed at improving hip protector use among nursing care facility residents. Design, Setting and Participants A cluster randomized controlled trial with 234 residents older than 75 years from 9 units of 7 nursing care facilities in the Northern Sydney region, Australia. Intervention Residents were cluster randomized in 3 groups. The first group received hard shell hip protectors without cost (no cost group). The second group received an educational session, a demonstration of the use of hip protectors, and free choice of type of hip protectors without cost (combined group). The third group was the control group who received a brochure about hip protectors. Measurements Primary outcome was adherence with the use of hip protectors at 3 and 6 months after recruitment. Secondary outcomes were falls, injuries, and fractures. Results No participants in the control group purchased hip protectors at any stage. At 3 months, 33% of participants in the no cost group and 27% in the combined group wore a hip protector at the time of visit. This declined to 25% and 24% respectively at 6 months. No significant difference was seen in any of the 3 adherence outcomes between the 2 intervention groups. The number of falls or hospitalizations did not differ between groups, with 5 hip fractures reported during the intervention period. Residents were more likely to be adherent if they were female and had greater restriction in daily activities. Conclusion Providing free hip protectors to older people living in nursing care facilities was necessary to increase initial acceptance and adherence. Nevertheless, after 6 months the achieved level of adherence was not high enough to be associated with a reduction of hip fractures. The provision of educational sessions and demonstrations to nursing staff and participants had no added value in this trial.

To compare the clinical outcomes and length of stay (LOS) between delirious patients with hyperactive symptoms admitted directly and those admitted indirectly from Emergency Department into a secured, behavioral unit jointly used by geriatricians and pyschogeriatricians (the Unit). A retrospective study analyzing data from the medical records of 122 patients with an admission diagnosis of delirium with hyperactive symptoms and subsequently discharged from the Unit, including restraint, one-to-one nursing care, falls, absconding, duration of delirium, recovery from delirium, destination and LOS. Significantly fewer patients with direct admission (n=68) required physical restraint or chemical restraint compared with those transferred (n=54). Patients admitted directly showed a higher discharge rate back home, shorter LOS, shorter duration of delirium and a higher rate of recovery from delirium than transferred patients. Of the transferred patients, more received one-to-one nursing care before transfer than after transfer. Three (5.6%) absconded before transfer, but none absconded from the Unit. The falls rate reduced from 14.2 to 6.7 falls/1000 patient delirium days after transfer. Delirious patients with hyperactive symptoms admitted directly to the Unit fared better in clinical outcomes and LOS. They also required less restraint, less intensive nursing and were unlikely to abscond compared to those transferred.

Our aim was to characterise PARK2 mutations and clinical features in Hong Kong Chinese with early-onset Parkinson’s disease. Subjects were recruited from two major hospitals. Detailed data included demographics, age of onset, duration of disease, neurological manifestations, complications and disease severity. Genetic analysis for PARK2 mutations was performed. Thirty-four patients were recruited (mean age of onset = 39 years; mean duration of disease = 10 years). Seven patients reported a family history. The salient clinical manifestations were resting tremor (33/34), bradykinesia (33/34), rigidity (30/34), postural instability (20/34), good response to l-dopa (33/34), asymmetry at onset (31/34) and sleep benefit (12/34). Motor complications were reported in a significant number of patients, and depression was the most common nonmotor complication. Five patients were identified to have PARK2 mutations. Two sisters were compound heterozygotes for an insertion and a deletion, a novel and rare 1 bp insertion/nonsense mutation c1378_1379insG (exon 12) and the entire deletion of exon 7. Another patient was homozygous for the entire deletion of exon 6. Two carriers were identified, one with a T1321C (Cys441Arg) missense mutation in exon 12 and another with a snp within intron 4. Our study reviewed a higher prevalence of PARK2 mutations in Chinese than that previously documented. A compound heterozygous mutation within two sisters with significant differences in age of onset and phenotypic manifestations suggest that modifier affects may be present in this family.

To evaluate the incidence of stroke, risk factors for stroke, and outcomes in elderly stroke patients with delirium.Cohort study with 12-month follow-up.Bankstown-Lidcombe Hospital, a 450-bed teaching hospital of the University of New South Wales, Sydney, Australia.One hundred fifty-six stroke patients aged 65 and older recruited over 1 year.Incidence of delirium (defined in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria) within 3 days poststroke, length of hospital stay, discharge destination, short- and long-term mortality, Functional Independence Measure (FIM) scores, and Mini-Mental State Examination (MMSE) scores.Thirty-nine (25%) elderly stroke patients had delirium within 3 days after stroke. Logistic regression analysis found that older age (P=.04), hemorrhagic stroke (P=.02), metabolic disorders (P=.003), dementia prestroke (P=.02), Glasgow Coma Scale (GCS) score less than 15 on admission (P.001), and inability to lift both arms on admission (P=.03) were independent predisposing factors for delirium. Patients who had a cardioembolic stroke (odds ratio (OR)=5.58) or total anterior circulation infarction (OR=3.42) were also more likely to develop delirium. Patients with delirium were associated with higher 6- and 12-month mortality (P.05), lower 12-month FIM and MMSE scores, and a higher 12-month institutionalization rate.Delirium occurred frequently in acute stroke patients aged 65 and older. Factors independently associated with delirium included old age, intracerebral hemorrhage, metabolic factors, prestroke dementia, initial GCS less than 15, and inability to lift both arms on admission. Patients with delirium had higher long-term mortality and a worse functional outcome.

We assessed the hypothesis that having a non-English-speaking background (NESB), being very elderly, living alone, and having cognitive impairment were contributing factors to anticoagulant under-utilisation for atrial fibrillation in our local community. A questionnaire was mailed to 532 general practitioners (GPs) in three areas of metropolitan Sydney, Australia. The questionnaire included five case scenarios, regarding either an English-speaking background (ESB) patient, or an NESB patient, each characterised by potential barrier(s) for anticoagulant usage: being (1) elderly; (2) elderly with mild dementia; (3) elderly with mild dementia and living alone; (4) elderly with severe dementia; and (5) very elderly. The overall response rate was 34%. The percentage of GPs recommending anticoagulation was 57%, 50%, 6%, 25% and 23%, respectively, for the ESB scenario, and 48%, 32%, 4%, 14% and 18%, respectively, for the NESB scenario. Eighty-eight percent of GPs rated 'adherence to International Normalized Ration monitoring' as 'very important' in their decision. In conclusion, the factors proposed in our hypothesis were associated with a lower likelihood for anticoagulant prescription for atrial fibrillation.

Background: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease. Methods: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined. Results: APOE ɛ2 and ɛ4 homozygotes were increased in stroke (4.5% vs. 1.0%, p=0.008), while in myocardial infarction the ɛ4 allele was increased (12.6% vs. 9.5%, p=0.006) but ɛ2 was decreased (3.7% vs. 12.1%, p=0.000006). For subjects with either APOE ɛ2 or ɛ4 alleles, LPL X alleles were increased in vascular disease (OR=2.2, p=0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies. Conclusion: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke.

Objectives – To examine 12-month outcomes and develop predictive models for outcomes in elderly stroke patients. Methods – Prospective study of 186 consecutive acute stroke patients aged ≥65 years admitted to a local hospital between March 2002 and March 2003. Outcome measurements included mortality, functional independence measure (FIM) score and nursing home placement. Two predictive models, using multiple logistic regression analysis, were developed to identify the factors associated with (i) mortality, and (ii) being alive and independent (defined as mean FIM score ≥90) at 12 months. Results – One hundred and seventy two (92%) patients were followed up at 12 months post-stroke. Mortality rate was 31%, and was significantly higher in nursing home vs non-nursing home origin patients (68% [15/22] vs 25% [38/150]). Nursing home placement for non-nursing home origin survivors was 28% (31/112). Age ≥85 years was associated with higher mortality (odds ratio = 5.3, 95% confidence interval = 1.8–15, P

We studied a variable number tandem repeat polymorphism within the dopamine transporter gene (DAT) for an association with Parkinson's disease in a Chinese population. Five alleles were detected, consisting of 6, 8, 9, 10, and 11 copies of the 40 base pair repeat sequence. The 10-copy allele was most common, accounting for 90% of alleles. There were no significant differences between the patients and the control subjects in the distribution frequencies of the alleles or genotypes. Therefore, this polymorphism is not associated with Parkinson's disease in Chinese populations.

Objectives: Paraoxonase (PON1), an enzyme associated with high-density lipoprotein (HDL) particles, inhibits oxidation and atherogenesis. We sought to investigate the association of the PON1 Q192R polymorphism with stroke and heart disease. Design and methods: In a case control study, we genotyped 242 ischemic stroke, 231 myocardial infarction (MI), and 310 healthy control subjects, all Chinese. Results: R-containing genotypes (R+) were associated with vascular disease, OR = 1.5, P = 0.03. RR was increased in MI patients who were either smokers (OR = 3.1, P = 0.01), male, or younger than 60. R+ but not RR genotypes were increased in stroke patients, particularly large artery type (OR = 2.6 and P = 0.02 for R+, OR = 1.0 for RR) or among smokers. The relative dearth of RR in stroke might be due to earlier MI or death in at-risk people, such as smokers. R+ genotypes were increased with stroke in hypertensive (OR = 2.1, P = 0.02) but not normotensive (OR = 1.0) subjects. Conclusions: PON1 192R+ genotypes were associated with stroke and MI, particularly in subsets of patients, in patterns suggesting a possible survivor effect.

Background MDR1 , a multidrug transporter, encodes a P-glycoprotein that regulates the bioavailability of xenobiotics and is highly expressed at the blood-brain-barrier. Two single nucleotide polymorphisms (SNPs) (e21/2677[G/T/A] and e26/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and function. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. Objective To determine whether specific haplotypes formed by SNPs e21/2677 and e26/3435 may protect against Parkinson disease (PD) among ethnic Chinese in Hong Kong. Design Case-control study. Setting Tertiary referral centers in Hong Kong. Subjects One hundred eighty-five patients with PD and 206 control subjects. Interventions The two SNPs were amplified in a single multiplex polymerase chain reaction. Five other SNPs that span 100 kilobases of the gene were also analyzed. Main Outcome Measures Haplotypes frequencies, degree of haplotype association with the disease status, and estimated odds ratio for each haplotype with associated 95% confidence intervals. Results In addition to 2677 G→T/A (exon 21) and 3435 C→T (exon 26), the other SNPs that were analyzed were –41 A→G (intron –1), –145 C→G (exon 1), –129 T→C (exon 1), 1236 T→C (exon 12), and 4036 A→G (exon 28). Haplotypes containing SNPs e21/2677 and e26/3435 were found to be significantly associated with risk of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD ( P 2 = 14.521; odds ratio, 0.33; 95% confidence interval, 0.19-0.59). Conclusions An MDR1 haplotype containing SNPs e21/2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.

Parkinson’s disease (PD) is the second mostcommon neurodegenerative disorder. Its preval-ence rises sharply after the sixth decade. Parkin-sonism is also common in the elderly. The study byBennet et al., found 15% of people aged 65–74,30% of those aged 75–84 and 50% of those aged 85and over had one or more parkinsonian signs (1).With an ageing population in developed countries,PD and parkinsonism will become more prevalentand important.An Australian epidemiological study publishedin 1966 (2) reported that the PD prevalence inAustralia was 66 per 100,000, which was muchlower than other developed countries (with theexception of Japan). The prevalence of PD in theUnited States of America, Europe and SouthAmerica has been consistently reported between150 and 300 per 100,000 (3). Since the survey in1966, the Australian population has aged signifi-cantly and the life expectancy at birth (both sexescombined) is now 79.2 years compared with70.9 years in 1965 (4).A pilot study in Randwick municipality ofSydney, Australia, from 1998 to 1999 revealedthat PD prevalence is substantially higher nowthan that reported in 1966 (5). The estimatedprevalence of PD (including newly diagnosedcases) in the Randwick community was 775 per100,000. If newly diagnosed cases were excluded,the prevalence would still have been as high as449 per 100,000. In contrast to the 1966 study(2), which used a general practitioner (GP)questionnaire, the Randwick survey used a two-step method with a screening phase followed byan examination phase. This difference in studymethodology may provide an explanation for thelower prevalence found in 1966 in that mildercases may not have presented to GPs in theearlier study, thus underestimating the true pre-valence of PD.The sample in Randwick was randomly chosenand although 2820 households were door-knocked,the eligible number (aged ‡55 years) involved inthe pilot study was small (n ¼ 527). Hence it wasdecided to repeat the study in another localgovernment area (LGA) of Sydney using thesame methodology. The new study was performedin Bankstown LGA.

To examine major bleeding and mortality rates of low molecular weight heparin (LMWH) and unfractionated heparin (UFH) for patients with pulmonary embolism (PE) and/or deep vein thrombosis (DVT), a retrospective review of the medical records for 286 patients who presented at a local hospital with PE and/or DVT during the period November 2002-August 2003 was performed.presence of co-morbidities, concurrent medications, presence, site and severity of bleeding, outcome. Of all the patients, 50.7% received LMWH plus warfarin, 21.0% received UFH plus LMWH plus warfarin, 14.0% received UFH and warfarin, and 9.8% received LMWH only. There were nine minor bleeds and six major bleeds, which resulted in four deaths. Being a hospitalized patient and being ageor =70 years were associated with a major bleed (p0.05). For hospital inpatients ageor =70 years on UFH and LMWH the number of major bleeds/1000 patient days was 18.9 and 9.2, respectively. The major bleeding rate is comparable if not better than that reported in the literature in our hospital setting where nearly half of the anticoagulation services were provided as ambulatory care. The increased rate of bleeding in the elderly we found is consistent with the findings of previous studies.

The 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene 677C --T polymorphism causes an A222V amino acid change which affects MTHFR enzyme activity and can increase homocysteine, a vascular disease risk factor. This polymorphism was examined for association with stroke. In a case-control study of 241 ischemic stroke patients and 304 controls in Hong Kong, the V allele increased in stroke [28% vs. 20%, odds ratio (OR) 1.5, p=0.003]. A lack of significance for the increase in the VV genotype (7.5% vs. 4.6%, OR 1.7, p = 0.16) may be due to its rarity in this region. V -allele carriers had more severe strokes (according to the NIH stroke scale). The association of the V allele with stroke occurred mostly in women or older subjects and was due to decreasing V allele frequency with age, as seen in other studies. This V frequency decline with age might be due to a loss of V -carrying controls from a higher risk of cancer, vascular disease, bone fracture, and kidney failure when folate is sparse. Examination of previous studies revealed that the association of VV genotype with stroke appeared stronger in Japan than elsewhere, possibly due to dietary differences. Perhaps folate supplementation for stroke prevention would particularly benefit VV individuals in such high-risk regions.

Parkinson disease (PD) is a neurodegenerative disorder that increases sharply after the sixth decade. There are many disorders in the elderly that exhibit some parkinsonian signs that can be confused with PD.This article discusses the diagnostic and management issues of PD in the elderly patient.Levo-dopa (L-dopa) therapy is the cornerstone of treatment for PD in the elderly. After 5-8 years of treatment, monitor complications such as fluctuations and dyskinesia usually occur and adjunct therapy may be required. Dopamine agonists can be used to smooth out motor fluctuations and amantadine is sometimes useful for dyskinesia. However, the adverse drug effects of adjunct therapy in the elderly are more common than with L-dopa alone, and risks need to be weighed up against benefits. Nonmotor complications including dementia, psychosis, depression, autonomic dysfunction and somnolence are common and require special attention. Late stage problems such as aspiration, difficulties with activities of daily living or recurrent falls require a multidisciplinary approach. Anticholinergic drugs such as benztropine and benzhexol are best avoided because of the high risk of major side effects.

Background: over 60% of older people have at least one admission to hospital in their last year of life, with themajority of people having multiple admissions. In Bankstown, New South Wales, Australia, we have a diverse ethnicand cultural population. We were interested in bed utilisation, documentation, and follow through of ‘care plans’ aswell as ‘not for resuscitation’ orders in the last year of life of the older people in our area.Methods: we reviewed and collected data from the medical records of patients over 65 years of age who died in ourhospital. Reviewers included a medical registrar, a research officer and two geriatricians. We collected a wide range ofinformation pertaining to the 12 months before death. This included demographics, chronic illnesses, geriatricsyndromes, number of admissions, bed days, care plans, and not for resuscitation orders as well as other relevant data.Results: 110 patients’ records were reviewed. The mean age was 80 years and 31% were from a non English-speakingbackground. The average number of admissions was 2.4 and the average number of bed days in the last year of life was25. Sixty-one of the patients had a care plan and a not for resuscitation order, 91% of which were written shortlybefore death. Using bi-variate analysis of old age (over 80), number of chronic illnesses, or geriatric syndromes present,the number of bed days was positively correlated to care plan and not for resuscitation orders. Logistic multivariateanalysis of chronic illnesses revealed that stroke (P=0.024) as well as stroke and fracture (P=0.008) were stronglycorrelated with care plan and not for resuscitation orders. Only 8 patients had an advanced care plan documentedprior to last admission. When advanced care plans were documented, they were generally clearly written and followedthrough appropriately (7 out of 8).Conclusion: this study showed that in our diverse population there were multiple admissions and utilisation ofhospital beds for older people in their last year of life. Care plans and not for resuscitation orders were rarelydocumented prior to last admission. However, when advanced care plans were done, they were usually welldocumented and followed through appropriately.Keywords: care plans, older people, last-year-of-life

Background Selective olfactory deficits occur in 70% to 90% of patients with Parkinson disease, independent of disease severity and duration. Olfactory testing may be a useful diagnostic aid for Parkinson disease, but the types of odors most commonly affected need to be identified. Objective To determine the pattern and types of odors affected in Parkinson disease by means of the University of Pennsylvania 12-item Brief Smell Identification Test (B-SIT; Sensonics, Inc, Haddon Heights, NJ). Design Testing patients with Parkinson disease and control subjects in 5 movement disorder clinics. Participants Forty-nine nondemented patients with Parkinson disease and 52 age- and sex-matched controls. Main Outcome Measures Normal or abnormal olfactory function was determined in each subject according to predetermined age and sex norms. Predictive statistics and discriminant function analyses were performed to determine the pattern and types of odors best discriminating patients from controls. Results Abnormal olfactory function was present in 40 (82%) of patients compared with 12 (23%) of controls. The B-SIT score was unaffected by smoking behavior, disease duration, or severity. The sensitivity of the B-SIT for Parkinson disease was 0.82, with a specificity and predictive value of 0.82 and 0.77, respectively. Only 5 of the 12 B-SIT odors (gasoline, banana, pineapple, smoke, and cinnamon) were required to adequately discriminate patients with Parkinson disease from controls. Conclusions With the use of the B-SIT, 5 specific odors appear primarily affected in patients with Parkinson disease. Significantly, the ability of patients to detect some odors was unimpaired compared with that of controls. Better diagnostic aids could be developed on the basis of the selective pattern of hyposmia observed in Parkinson disease.

Objective: To find out if patients with chronic illnesses living in the community are at risk of unplanned hospital admissions through emergency departments; what types of chronic illnesses may be putative risk factors; and if an increase in the number of chronic illnesses may be associated with increased risk. Methods: The survey included the completion of a standardized questionnaire for medical illnesses in a random sample of older people dwelling in the community and analysis of admission records to our hospital. The principal diagnoses for admissions were recorded. The risk factors for admissions were analysed. Results: Five hundred and twenty-six (239 men and 287 women) people aged 55 years and over were interviewed. Musculoskeletal disorders, hypertension, gastrointestinal disorders and ischaemic heart disease were the most frequently reported of the chronic illnesses surveyed. A total number of 70 people from the survey group with a total of 115 admissions through emergency departments were recorded. Using logistic regression model, hypertension, ischaemic heart disease and age were found to be risk factors for emergency admissions amongst this group of community-dwelling residents. The ratios were 2.03 (95% confidence interval (CI): 1.2–3.44), 2.02 (95% CI: 1.16–3.49) and 1.05 (95% CI: 1.02–1.09), respectively. Furthermore, multiple (three or more) chronic illnesses were found to be a strong predictor of hospital admission via emergency department (chi-square = 16.647, DF = 1, P-value < 0.001). Conclusion: We conclude that there was significant association between multiple chronic diseases and emergency admissions for older people. Of these, hypertension and ischaemic heart disease were found to be significant predictors. Age per se was found to be of borderline significance.

To evaluate the advantages of comprehensive therapy for acute stroke in a stroke unit.The data of 207 acute stroke patients treated in a stroke unit in Australia (group A) were compared with those of 326 acute stroke patients treated in our neurological ward (group B). They were diagnosed by CT or MRI and found to have hemiplegia in 48 hours.There were significant differences between group A and group B in mortality within 14 days (5.3% vs 10.4%), rate of non-cerebral causes of death (27.3% vs 64.7%) and rate of infection (17.9% vs 47.9%), P0.01. Moreover the scores of Europe Stroke Scale at 21 days and Modified Rankin Scale at 90 days were significantly different between the two groups (P0.01).Prognosis of acute stroke patients managed by comprehensive therapy in stroke unit was superior to that treated conventionally in neurological ward.

Parkinson’s disease is a common neurological disease and its prevalence increases with age. Because of an ageing population and changing environment compared to the last epidemiological study done in Australia over 30 years ago, we have conducted a door-to-door pilot survey which looked at the latest prevalence as well as putative risk factors in a random population. We used a two-phase investigation method (screening followed by detailed examination) in a random community sample of 2,820 households (with 527 individuals aged 55 and over) along with 203 residents in aged care facilities (single-phase examination for residents aged 55 and above) in the Randwick area of Sydney, New South Wales. We had a 75% participation rate in the community and a 94% in the aged care facilities. The results of the survey in this sample of 730 subjects indicated that the crude prevalence of Parkinson’s disease was between 3.6 and 4.9% (higher in the aged care facilities). The putative risk factors positively identified using chi-square method were ‘family history’ (p < 0.01) and ‘exposure to chemicals at work or in surrounding environment’ (p < 0.05). The age-adjusted prevalence rate of Parkinson’s disease revealed at least a 42.5% increase in the disease compared to 1966. We conclude that there may be an increase in the disease in Australia due to ageing and other risk factors.

Apart from very few families who have a direct cause from genetic mutation, causes of most Parkinson's disease (PD) remain unclear. Many allelic association studies on polymorphism of different candidate genes have been studied. Although these association studies do not imply a causal relationship, it does warrant further studies to elucidate the pathophysiologic significance. CYP1A1 polymorphisms have been reported to be associated with PD in a Japanese population sample. Since CYP1A1 transforms aromatic hydrocarbons into products that may be neurotoxic and perhaps lead to PD, we therefore undertook a study to look at the possible association of CYP1A1 polymorphism and PD in a Chinese population. Contrary to the Japanese result, we did not find any statistically significant difference between the PD group and the control group in our study with a bigger sample size.

Parkinson's disease is a common neurodegenerative disorder in elderly people. Epidemiological studies of the disease can be labour intensive. A two phase design including a screening questionnaire as the first phase has become a popular method in prevalence studies of Parkinson's disease. Such a design has many advantages including less work for assessing physicians and enhanced recruitment of people to be screened. However, its wider application may be questioned because validation has been limited to samples that are drawn from hospitals (or clinics) and may be inappropriate for a community setting. This study assesses whether validating screening questionnaire by using a hospital sample yields the same result as a community based sample. Furthermore, it seeks to establish whether the screening instrument can be simplified to involve less questions. The findings show that some of the questions used in the screening phase yield different responses when comparing a hospital group with a community group. This study also provides a simplified model of questions that may be relevant for screening in the community setting.

To study the Ala53Thr and Ala30Pro mutations of the alpha-synuclein gene in a large number of Chinese patients with Parkinson disease (PD) as well as controls.We recruited 183 Chinese patients with sporadic PD, 17 with younger-onset PD (onset age50 years), and 7 with PD and a positive family history as well as 227 unaffected Chinese control subjects from the outpatient departments of 2 major hospitals in Hong Kong. All subjects were assessed for the the diagnosis of PD by a consultant neurologist or geriatrician. Subjects were interviewed with a standard questionnaire that also questioned for family history. Venous blood samples were obtained from the subjects and genomic DNA was extracted and studied for the presence of Ala53Thr mutation in exon 4 and Ala30Pro mutation in exon 3 of the alpha-synuclein gene using a polymerase chain reaction restriction fragment length polymorphism method.None of the Chinese PD patients or controls had either the Ala53Thr (exon 4) or Ala30Pro (exon 3) mutation of the alpha-synuclein gene.We failed to discover Ala53Thr or Ala30Pro mutations in a large number of Chinese patients with PD and control subjects, adding to the emerging consensus that variations in the alpha-synuclein gene are associated with PD in few families worldwide.

Monoamine oxidase B (MAOB) metabolises dopamine and activates neurotoxins known to induce parkinsonism in humans and primates. Therefore the MAOB gene (MAOB; Xp15.21–4) is a candidate gene for Parkinson’s disease (PD). Longer length dinucleotide repeat sequences in a highly polymorphic GT repeat region of intron 2 of this gene showed an association with PD in an Australian cohort. We repeated this allele-association study in a population of 176 Chinese PD patients ¶(90 men, 86 women) and 203 age-matched controls (99 men, 104 women). Genomic DNA was extracted from venous blood and the polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis. There was no significant difference in allele frequencies of the (GT) repeat allelic variation between patients and controls (χ2 = 2.48; df = 5, P < 0.75). Therefore the longer length GT repeat alleles are not associated with PD in this Chinese population. Possible reasons for the discrepancy between Chinese and Australian populations include a different interaction between this genetic factor and environmental factors in the two populations and the possibility that the long length GT repeat alleles may represent a marker mutation, genetically linked to another susceptibility allele in whites but not in Chinese. Methodological differences in the ascertainment of cases and controls in this cohort could also explain the observed differences. Further study is required to determine whether the longer length GT repeat alleles are true susceptibility alleles in PD.

The deletion allele (D allele) polymorphism in the angiotensin converting enzyme (ACE) gene is associated with increased levels of the neuropeptide substance P in the basal ganglia and substantia nigra. A reduction of substance P levels in the brain occurs in Parkinson’s disease (PD) and has been implicated in the pathogenesis of the disease. We investigated the hypothesis that the D allele may be protective towards PD by examining the frequency of the ACE (I/D) polymorphism in 178 PD cases (male:female ratio = 1.4) and 192 controls (male:female ratio = 1.5). ACE (I/D) genotype was determined using polymerase chain reaction and 3% agarose gel electrophoresis. Unadjusted chi-square analysis revealed no significant difference between genotype frequencies (χ2 = 3.30, p > 0.10) or allele frequencies (χ2 = 2.52, p > 0.10) between patient and control groups, although PD patients were less likely to be homozygous (OR = 0.80, 95% CI = 0.49–1.29) or heterozygous (OR = 0.80, 95% CI = 0.59–1.06) for the D allele. A stepwise logistic regression analysis of the ACE deletion and risk factor data confirmed that there was no significant association between the ACE deletion (D allele) polymorphism and PD (OR = 0.62, 95% CI = 0.35–1.10, p = 0.10). This study does not support the hypothesis that the D allele of the ACE gene confers a protective effect with respect to PD.